There are many factors which can increase your risk of developing venous thromboembolism (deep vein thrombosis and pulmonary embolism). There are many different explanations or reasons for the formation of a blood clot, which is called a ‘provoked’ venous thromboembolism (VTE). Here are some examples:

• Pregnancy.
• Oral contraceptives.
• Hormone replacement therapy (HRT).
• Over 60 years of age.
• Being overweight or obese.
• Cancer.
• Family history.
• Genetics – disorders which affect blood clotting factors (for example factor V Leiden).
• Sitting for a long time – driving, flying or hospitalisation.
• Any activity when your legs remain still for hours, and your calf muscles don't contract.

There are also situations that are unexplained or have no known causes. A blood clot in a vein can occur with no apparent underlying risk factor. This is called an ‘unprovoked’ VTE.

As immobility is a common cause for VTE, research recommends regularly stretching your legs and calves if sitting for extended periods of time. Studies suggest that regular exercise or physical activity can help prevent or reduce the risk of thrombotic events occurring. For each additional hour seated, without getting up and moving around, the risk of VTE increases by 20%. Those who have their own desk at work and regularly ate their lunch at their desk had a significantly higher risk.

There is also evidence of an association between exercise and an increased risk of VTE for certain population groups or circumstances. Research has shown that exercise intensity, age, clotting factors and specific sports have demonstrated a link.

Exercise intensity

Some studies have endeavoured to define the effects of a single session of exercise on haemostasis in healthy people. They have shown that, generally, there is a brief increase in blood coagulation, fibrinolytic activity and platelet accumulation and function, which may continue for up to 24 hours after exercise.

Exercise intensity appears to be a factor in whether these mechanisms are positive or negative. Moderate intensity apparently shifts the balance in support of finrinolysis (breakdown of fibrin or insoluble clotting protein in blood clots); and intense exercise is more likely to increase the rate and level of prothrombotic pathways. This process may also clarify the increased incidence of cardiovascular events that have been shown to occur during or after vigorous exercise.

This data should not be generally applied to everyone and every situation. There are a number of potential confounders which appear in the research, including age, gender, oral contraceptive use, regular physical activity and underlying health conditions. These are all associated with alterations in thrombotic risk.

Age

Research from 2010 found the risk for VTE increases in the elderly aged ≥60 years. Participants over the age of 60 who reported more than 3 hours of moderate to high intensity exercise per week had an elevated risk of VTE. Compared to inactivity, low levels of moderate exercise (<3 hours/week) tended to decrease the risk of VTE in those under the age of 60.

Factor VIII

Factor VIII is a coagulation factor, and levels have been found to increase with age and exercise. Increased levels with exercise also appear to persist during the recovery stage after exercise has ceased.

• Factor VIII levels increase with age, with an average rise of 5 to 6 IU/dL per decade. A study in 2021 of 401 women (58.5%) and men (41.5%), with an average age of 78 years, found a higher risk of venous thrombosis.
• High levels of factor VIII are a risk factor for a first thrombotic event, with an increased risk of recurrences, which may indicate that sustained anticoagulant treatment is needed in these patients.

Paget-Schroetter syndrome

Paget-Schroetter syndrome (PSS) is thrombosis provoked by effort or exertion. It is also referred to as the ‘effort thrombosis’. This is a rare condition and is more common in young healthy adults in their 20s and 30s; with a 2:1 male to female ratio. The incidence is approximately 1-2 per 100,000 per year. The syndrome is difficult to diagnose as there is usually no other relevant medical comorbidities.

The disorder is described as compression and subsequent thrombosis of the axillary (armpit) and subclavian veins at the thoracic outlet (space between the collarbone and first rib packed with blood vessels). Thrombosis is secondary to the repetitive overuse of the arm which leads to local inflammation, microtrauma and compression to the area.

This is also known as thoracic outlet syndrome (TOS), where there are three types.

• Neurogenic TOS – most common type.                                  Affects the brachial plexus nerves which come from the spinal cord and controls movements and feeling in the shoulder, arm and hand. Symptoms include numbness or tingling in arms or fingers; pain in the neck, shoulder, arm or hand; arm fatigue with activity; and weakening grip.
• Venous TOS – compression and damage to one or more veins below the collarbone, which can result in blood clots. Symptoms include discolouration of the hand or fingers; pain and swelling in the hand or arm.
• Arterial TOS – least common.                                                  Compression of the arteries underneath the collarbone causing a blood clot or aneurysm (dilatation or weakening an artery wall which supplies blood to a specific area causing it to bulge). Symptoms include pulsating lump near the collarbone; cold fingers, hands or arms; pain in arm and hand; discolouration in one or more fingers; weak or no pulse in arm.

As the condition affects the upper body (axillary and subclavian veins), another term used for PSS is upper extremity deep vein thrombosis (UEDVT). In 2012, a review found that UEDVT accounted for approximately 10% of cases of DVT. Paget Schroetter syndrome or UEDVT commonly affects athletes or individuals who exercise extensively or perform activities which involve continuous overhead motions, also including occupations like painting or car repair work.

The sports mainly associated with PSS, which include repetitive over-the-head motion of the arms are baseball/softball pitchers, badminton, swimmers, rowers or weightlifters. The syndrome commonly occurs in otherwise healthy young men who report, before the onset of thrombosis, where they were undertaking vigorous arm exercises or activities.

Case reports

There are several studies investigating the motive or reason why some individuals develop sudden cardiac issues or thrombus formation during or after exercise. Here are a few examples:

• A young 21-year-old football player developed chest pain during an exercise session, while bench-pressing 400lbs. He was diagnosed with an acute myocardial infarction (MI). A coronary arteriogram test showed a thrombus blocking the proximal left anterior descending artery (a branch of the left coronary artery that supplies blood to part of the heart). Five months later, similar symptoms occurred while lifting heavy weights, and again he had another acute MI. All other arteries were normal and an ultrasound found no lower extremity DVT. After a full hypercoagulable workup was carried out, Factor VIII levels were found to be extremely elevated.
• A 37-year-old active judo tutor went to his GP when he noticed redness and swelling of his right arm and elbow after a normal exercise session. When there was no improvement, he went to the hospital. After medical staff ruled out bursitis and cellulitis, an ultrasound revealed a right axillary DVT with extension into the cephalic and brachial veins. He was given antibiotics and low molecular weight heparin while waiting further investigation. After another review of his case, he was diagnosed with PSS and underwent immediate thrombolysis to clear his extensive thrombosis.
• A 41-year-old man developed redness, swelling and pain in his upper arm 7 days after playing badminton. He was diagnosed with PSS.
• A 16-year-old male rugby player had discomfort in the right axilla (armpit) for two weeks after participating in intensive weight training. He continued to exercise which resulted in swelling of his right arm, swollen veins in his right upper arm, axilla and chest wall. An ultrasound found complete thrombosis of the right subclavian axillary vein.
• An 18-year-old female freestyle-swimmer was diagnosed with PSS after presenting with pain and dysfunction of the arm.

A research review in 2020 found the following statistics after reviewing 123 cases of PSS.

Baseball – 26.8%; 70% being pitchers. Weightlifting – 19%. Swimming – 13%. American football – 9.8%. Basketball – 5.7%. Volleyball – 3.3%. The average time from symptom onset to diagnosis was 13.4 days. It took approximately 4.7 months for the athletes to return to the sport. Complications were reported in 26.7% of participants; with pulmonary embolism being the most common. A small group (1.6%) noted persistent pain and discomfort.

Andrew Gaze is a Thrombosis Australia ambassador

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References

• Thoracic outlet syndrome - Symptoms and causes - Mayo Clinic
• Paget-Schroetter Syndrome - StatPearls - NCBI Bookshelf (nih.gov)
• F8 gene: MedlinePlus Genetics
• https://www.mayoclinic.org/diseases-conditions/deep-vein-thrombosis/symptoms-causes/syc-20352557
• https://www.stoptheclot.org/about-clots/athletes-and-blood-clots/
• Adams, M., Fell, J. & Williams, A. (2009). Exercise causing thrombosis. The Physician and Sports Medicine, 37(4): 124-130. Doi:10.3810/psm.2009.12.1750.
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• Kamphuisen, P.W., Eikenboom, J.C.J., and Bertina, R.M. 2001. Elevated Factor VIII Levels and the Risk of Thrombosis. Arteriosclerosis, Thrombosis and Vascular Biology 21. 731-738. https://doi.org/10.1161/01.ATV.21.5.731.
• Miyamori, T.H. et al. (2020). Two patients with Paget-Schroetter syndrome that were successfully diagnosed by doppler ultrasonography: case studies with a literature review. Intern Med; 59(20): 2623-2627. Doi:10.2169/internalmedicine.4349-20.
• Roche-Nagle, G., Ryan, R., Barry, M., & Brophy, D. (2007). Effort thrombosis of the upper extremity in a young sportsman: Paget-Schroetter syndrome. Br J Sports Med. 41(8):540-1. Doi:10.101136/bjsm.2006.033456.
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